Oral care products comprising tetrabasic zinc chloride and trimethylglycine

ABSTRACT

The invention provides oral care compositions comprising a mixture of tetrabasic zinc halide and trimethylglycine, in free or orally acceptable salt form. Methods of making and using the compositions are also provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a United States National Stage Application under 35U.S.C. §371 of International Application PCT/US2012/070528, filed onDec. 19, 2012, the contents of which is hereby incorporated by referencein its entirety.

BACKGROUND

Dental erosion involves demineralization and damage to the toothstructure due to acid attack from nonbacterial sources. Erosion is foundinitially in the enamel and, if unchecked, may proceed to the underlyingdentin. Dental erosion may be caused or exacerbated by acidic foods anddrinks, exposure to chlorinated swimming pool water, and regurgitationof gastric acids. The tooth enamel is a negatively charged surface,which naturally tends to attract positively charged ions such ashydrogen and calcium ions, while resisting negatively charged ions suchas fluoride ions. Depending upon relative pH of surrounding saliva, thetooth enamel will lose or gain positively charged ions such as calciumions. Generally saliva has a pH between 7.2 to 7.4. When the pH islowered and concentration of hydrogen ions becomes relatively high, thehydrogen ions will replace the calcium ions in the enamel, forminghydrogen phosphate (phosphoric acid), which damages the enamel andcreates a porous, sponge-like roughened surface. If saliva remainsacidic over an extended period, then remineralization may not occur, andthe tooth will continue to lose minerals, causing the tooth to weakenand ultimately to lose structure.

Dentinal hypersensitivity is acute, localized tooth pain in response tophysical stimulation of the dentine surface as by thermal (hot or cold)osmotic, tactile combination of thermal, osmotic and tactile stimulationof the exposed dentin. Exposure of the dentine, which is generally dueto recession of the gums, or loss of enamel, frequently leads tohypersensitivity. Dentinal tubules open to the surface have a highcorrelation with dentine hypersensitivity. Dentinal tubules lead fromthe pulp to the cementum. When the surface cementum of the tooth root iseroded, the dentinal tubules become exposed to the external environment.The exposed dentinal tubules provide a pathway for transmission of fluidflow to the pulpal nerves, the transmission induced by changes intemperature, pressure and ionic gradients.

Heavy metal ions, such as zinc, are resistant to acid attack. Zinc ranksabove hydrogen in the electrochemical series, so that metallic zinc inan acidic solution will react to liberate hydrogen gas as the zincpasses into solution to form di-cations, Zn²⁺. Zinc has been shown tohave antibacterial properties in plaque and caries studies.

Soluble zinc salts, such as zinc citrate, have been used in dentifricecompositions, see, e.g., U.S. Pat. No. 6,121,315, but have severaldisadvantages. Zinc ions in solution impart an unpleasant, astringentmouthfeel, so formulations that provide effective levels of zinc, andalso have acceptable organoleptic properties, have been difficult toachieve. Finally, the zinc ions will react with anionic surfactants suchas sodium lauryl sulfate, thus interfering with foaming and cleaning.

Tetrabasic zinc chloride (TBZC), is a zinc hydroxy compound withchemical formula Zn₅(OH)₈Cl₂.H₂O. It is also referred to as zincchloride hydroxide monohydrate, basic zinc chloride, zinchydroxychloride, or zinc oxychloride. It occurs naturally as the mineralsimonkolleite. Unlike zinc chloride, TBZC is insoluble in water. TBZChas been suggested for use in oral care compositions, see e.g.,GB2243775A, but such formulations do not deliver zinc efficiently to theteeth due to the insolubility of TBZC.

N,N,N-trimethylglycine (TMG or glycine betaine) is a quaternary aminoacid. At neural pH, the compound exists as a zwitterion, forming aninner salt between the quaternary ammonium and the carboxy portions ofthe molecule. In the presence of strong acids, it will form acidaddition salts, e.g., hydrochloride. The compound is originally isolatedfrom sugar beets, and is used as a dietary supplement in animal feed andas a laboratory reagent stabilizer, e.g., in polymerase chain reactions.There are reports of its use in oral care products to treat dry mouth,e.g. U.S. Pat. No. 6,156,293, and in antiperspirant products, e.g. U.S.Pat. No. 6,969,510.

While the prior art discloses the use of various oral compositions forthe treatment of dentinal hypersensitivity, dental caries, and enamelerosion and demineralization, there is still a need for additionalcompositions and methods which provide improved performance in suchtreatments.

SUMMARY

While TBZC is substantially insoluble in prior art formulations, it hasnow been discovered that tetrabasic zinc chloride can form a solublecomplex with TMG in both its free form and acidified form. When placedin formulation, this complex provides an effective concentration of zincions to the enamel and/or dentine surface, thereby protecting againsterosion, reducing bacterial colonization and biofilm development, andproviding enhanced shine to the teeth. Moreover, upon dilution duringuse, the formulation provides a precipitate which can plug the dentinaltubules, thereby reducing the sensitivity of the teeth. This isunexpected, at least partially because better solubilization isgenerally expected with dilution. While providing efficient delivery ofzinc in comparison to conventional formulations with insoluble TBZC, theformulations comprising TBZC and TMG do not exhibit the poor taste andmouthfeel, poor fluoride delivery, and poor foaming and cleaningassociated with conventional zinc-based oral care products using solublezinc salts.

The formation of this soluble complex is particularly surprising, assimilar complexes are not formed between zinc and, for example, creatine(an amino acid with a basic guanidine moiety rather than an ammoniummoiety) or cetylpyridinium chloride, or acidified forms of the two. WhenTMG is present in its acidified form (such as in the form of TMGhydrochloride), the soluble complex accounts for a major component ofthe ionic species. When TMG is used in its free form, this solublecomplex can still form, but is minor amounts and rather insignificant inquantity relative to TMG monomers and oligomers. Without being bound bytheory, it appears that upon combination of TBZC and trimethylglycinehydrochloride in aqueous solution, two highly soluble species areformed—a complex comprising zinc, TMG and chloride and a second complexcomprising zinc and chloride. Upon further dilution of the solution,these complexes break down, and a precipitate principally comprisedzinc-containing compounds (such as TBZC, zinc hydroxide).

The invention thus provides in one embodiment, a complex comprising TBZCand TMG, in its free or acidified form, for example a zinc-TMG-HClcomplex, e.g., formed by combining TBZC and trimethylglycinehydrochloride in aqueous solution.

In a further embodiment, the invention provides oral care compositions,for example mouthwash, oral gel or dentifrice compositions, thatcomprise TBZC in combination with TMG, in its free or acidified form,e.g. that comprise a complex as described above. The compositions mayoptionally further comprise a fluoride source and or an additionalphosphate source. The compositions may be formulated in a suitable oralcare formulation e.g., a conventional dentifrice, oral gel or mouthwashbase, e.g., comprising one or more abrasives, surfactants, foamingagents, vitamins, polymers, enzymes, humectants, thickeners,antimicrobial agents, preservatives, flavorings, and/or colorants.

The invention further provides methods of using the compositions of theinvention to reduce and inhibit acid erosion of the enamel, clean theteeth, reduce bacterially-generated biofilm and plaque, reducegingivitis, inhibit tooth decay and formation of cavities, and reducedentinal hypersensitivity, comprising applying a composition of theinvention to the teeth. The invention further provides methods of usingthe compositions of the invention to whiten the teeth by imparting acoating onto the teeth, wherein the coating is whiter than the nativeteeth.

Further areas of applicability of the present invention will becomeapparent from the detailed description provided hereinafter. It shouldbe understood that the detailed description and specific examples, whileindicating the preferred embodiment of the invention, are intended forpurposes of illustration only and are not intended to limit the scope ofthe invention.

DETAILED DESCRIPTION

The following description of the preferred embodiment(s) is merelyexemplary in nature and is in no way intended to limit the invention,its application, or uses.

As used herein, “trimethylglycine” refers to N,N,N-trimethylglycine; andthe terms may be used interchangeably herein.

The invention therefore provides, in a first embodiment, an oral carecomposition (Composition 1), comprising or prepared from a mixture oftetrabasic zinc chloride (TBZC) and N,N,N-trimethylglycine (TMG) in freeor orally acceptable acid addition salt form; e.g.,

-   -   1.1. Composition 1 wherein the level of zinc in the formulation        by weight on an elemental basis is 0.25-4%, e.g., 1-2%, e.g.,        0.5-1.5%, e.g., about 1%.    -   1.2. Composition 1 or 1.1 wherein the TMG is provided in orally        acceptable acid addition salt form, e.g. hydrochloride salt        form, or where TMG is formed in situ by providing TMG and acid        (such as HCl) as separate entities in molar ratios between 1:5        to 5:1 (moles of TMG vs. moles of protons released from the        acid).    -   1.3. Any of the foregoing compositions wherein the molar ratio        of TBZC to TMG is from 1:1 to 1:10, e.g., about 1:5.    -   1.4. Any of the foregoing compositions wherein the molar ratio        of zinc to TMG is from 5:1 to 1:2, e.g., about 1:1.    -   1.5. Any of the foregoing compositions wherein the pH is between        pH 5 and pH 6.    -   1.6. Any of the foregoing compositions wherein the formulation        includes the step of combining TBZC and trimethylglycine        hydrochloride in aqueous solution.    -   1.7. Any of the foregoing compositions wherein the TMG is        provided in hydrohalide salt form, and the TBZC and TMG form        soluble complexes selected from zinc-TMG-halide complexes,        zinc-halide complexes, and mixtures thereof, e.g. wherein the        halide is selected from fluoride, chloride, bromide and mixtures        thereof    -   1.8. Any of the foregoing compositions wherein the TMG is        provided in hydrohalide salt form, and the TBZC and TMG form two        soluble complexes, one having the chemical composition Zn₂O₈H₆X₂        and the other having the chemical composition Zn₂O₈H₅X₂-TMG,        wherein X is selected from Cl, F, Br, and mixtures thereof    -   1.9. Any of the foregoing compositions wherein the TMG is        provided in hydrochloride salt form, and the TBZC and TMG form        soluble complexes selected from zinc-TMG-chloride complexes,        zinc-chloride complexes, and mixtures thereof.    -   1.10. Any of the foregoing compositions wherein the TMG is        provided in hydrochloride salt form, and the TBZC and TMG form        two soluble complexes, one having the chemical composition        Zn₂O₈H₆Cl₂ and the other having the chemical composition        Zn₂O₈H₅Cl₂-TMG.    -   1.11. Any of the foregoing compositions wherein a complex        comprising TBZC and TMG is formed, in whole or in part, in situ        after the composition is applied.    -   1.12. Any of the foregoing compositions wherein a complex        comprising TBZC and TMG is formed, in whole or in part, in situ        after the composition is formulated.    -   1.13. Any of the foregoing compositions comprising an acid,        e.g., hydrochloric acid, e.g., such that the pH of the        composition is between 5 and 6.    -   1.14. Any of the foregoing compositions, further comprising a        basic amino acid, e.g., lysine or arginine.    -   1.15. Any of the foregoing compositions, in a substantially        anhydrous carrier, e.g. a carrier comprising less than 10%        water.    -   1.16. Any of the foregoing compositions in the form of a        toothpaste, gel, mouthwash, powder, cream, strip, or gum.    -   1.17. Any of the foregoing compositions in an orally acceptable        base, e.g., a mouthwash, gel, or dentifrice base.    -   1.18. Any of the foregoing compositions in the form of a        dentifrice, e.g., wherein the TBZC and TMG are present in an        effective amount, e.g., in an amount of 0.05-4% zinc by weight,        e.g., about 0.5-3%, e.g. about 1% zinc by weight, in a        dentifrice base.    -   1.19. Composition 1.1, wherein the dentifrice base comprises an        abrasive, e.g., an effective amount of a silica abrasive, e.g.,        10-30%, e.g., about 20%.    -   1.20. Composition 1 in the form of a mouthwash, e.g., wherein        the TBZC is present in an effective amount, e.g., in an amount        of 0.05-4% of zinc by weight, e.g., about 1% of zinc by weight.    -   1.21. Any of the foregoing compositions further comprising an        effective amount of a fluoride ion source, e.g., providing 500        to 3000 ppm fluoride.    -   1.22. Any of the foregoing compositions further comprising an        effective amount of fluoride, e.g., wherein the fluoride is a        salt selected from stannous fluoride, sodium fluoride, potassium        fluoride, sodium monofluorophosphate, sodium fluorosilicate,        ammonium fluorosilicate, amine fluoride (e.g.,        N′-octadecyltrimethylendiamine-N,N,N′-tris(2-ethanol)-dihydrofluoride),        ammonium fluoride, titanium fluoride, hexafluorosulfate, and        combinations thereof.    -   1.23. Any of the preceding compositions comprising an effective        amount of one or more alkali phosphate salts, e.g., sodium,        potassium or calcium salts, e.g., selected from alkali dibasic        phosphate and alkali pyrophosphate salts, e.g., alkali phosphate        salts selected from sodium phosphate dibasic, potassium        phosphate dibasic, dicalcium phosphate dihydrate, calcium        pyrophosphate, tetrasodium pyrophosphate, tetrapotassium        pyrophosphate, sodium tripolyphosphate, and mixtures of any of        two or more of these, e.g., in an amount of 1-20%, e.g., 2-8%,        e.g., ca. 5%, by weight of the composition.    -   1.24. Any of the foregoing compositions comprising buffering        agents, e.g., sodium phosphate buffer (e.g., sodium phosphate        monobasic and disodium phosphate).    -   1.25. Any of the foregoing compositions comprising a humectant,        e.g., selected from glycerin, sorbitol, propylene glycol,        polyethylene glycol, xylitol, and mixtures thereof, e.g.        comprising at least 20%, e.g., 20-40%, e.g., 25-35% glycerin.    -   1.26. Any of the preceding compositions comprising one or more        surfactants, e.g., selected from anionic, cationic,        zwitterionic, and nonionic surfactants, and mixtures thereof,        e.g., comprising an anionic surfactant, e.g., a surfactant        selected from sodium lauryl sulfate, sodium ether lauryl        sulfate, and mixtures thereof, e.g. in an amount of from about        0.3% to about 4.5% by weight, e.g. 1-2% sodium lauryl sulfate        (SLS); and/or a zwitterionic surfactant, for example a betaine        surfactant, for example cocamidopropylbetaine, e.g. in an amount        of from about 0.1% to about 4.5% by weight, e.g. 0.5-2%        cocamidopropylbetaine.    -   1.27. Any of the preceding compositions further comprising a        viscosity modifying amount of one or more of polysaccharide        gums, for example xanthan gum or carrageenan, silica thickener,        and combinations thereof.    -   1.28. Any of the preceding compositions comprising gum strips or        fragments.    -   1.29. Any of the preceding compositions further comprising        flavoring, fragrance and/or coloring.    -   1.30. Any of the foregoing compositions comprising an effective        amount of one or more antibacterial agents, for example        comprising an antibacterial agent selected from halogenated        diphenyl ether (e.g. triclosan), herbal extracts and essential        oils (e.g., rosemary extract, tea extract, magnolia extract,        thymol, menthol, eucalyptol, geraniol, carvacrol, citral,        hinokitol, catechol, methyl salicylate, epigallocatechin        gallate, epigallocatechin, gallic acid, miswak extract,        sea-buckthorn extract), bisguanide antiseptics (e.g.,        chlorhexidine, alexidine or octenidine), quaternary ammonium        compounds (e.g., cetylpyridinium chloride (CPC), benzalkonium        chloride, tetradecylpyridinium chloride (TPC),        N-tetradecyl-4-ethylpyridinium chloride (TDEPC)), phenolic        antiseptics, hexetidine, octenidine, sanguinarine, povidone        iodine, delmopinol, salifluor, metal ions (e.g., zinc salts, for        example, zinc citrate, stannous salts, copper salts, iron        salts), sanguinarine, propolis and oxygenating agents (e.g.,        hydrogen peroxide, buffered sodium peroxyborate or        peroxycarbonate), phthalic acid and its salts, monoperthalic        acid and its salts and esters, ascorbyl stearate, oleoyl        sarcosine, alkyl sulfate, dioctyl sulfosuccinate,        salicylanilide, domiphen bromide, delmopinol, octapinol and        other piperidino derivatives, nicin preparations, chlorite        salts; and mixtures of any of the foregoing; e.g., comprising        triclosan or cetylpyridinium chloride.    -   1.31. Any of the foregoing compositions comprising an        antibacterially effective amount of triclosan, e.g. 0.1-0.5%,        e.g. about 0.3%.    -   1.32. Any of the preceding compositions further comprising a        whitening agent, e.g., a selected from the group consisting of        peroxides, metal chlorites, perborates, percarbonates,        peroxyacids, hypochlorites, and combinations thereof.    -   1.33. Any of the preceding compositions further comprising        hydrogen peroxide or a hydrogen peroxide source, e.g., urea        peroxide or a peroxide salt or complex (e.g., such as        peroxyphosphate, peroxycarbonate, perborate, peroxysilicate, or        persulphate salts; for example calcium peroxyphosphate, sodium        perborate, sodium carbonate peroxide, sodium peroxyphosphate,        and potassium persulfate);    -   1.34. Any of the preceding compositions further comprising an        agent that interferes with or prevents bacterial attachment,        e.g., solbrol or chitosan.    -   1.35. Any of the preceding compositions further comprising a        source of calcium and phosphate selected from (i) calcium-glass        complexes, e.g., calcium sodium phosphosilicates, and (ii)        calcium-protein complexes, e.g., casein phosphopeptide-amorphous        calcium phosphate    -   1.36. Any of the preceding compositions further comprising a        soluble calcium salt, e.g., selected from calcium sulfate,        calcium chloride, calcium nitrate, calcium acetate, calcium        lactate, and combinations thereof.    -   1.37. Any of the preceding compositions further comprising a        physiologically or orally acceptable potassium salt, e.g.,        potassium nitrate or potassium chloride, in an amount effective        to reduce dentinal sensitivity.    -   1.38. Any of the foregoing compositions further comprising an        anionic polymer, e.g., a synthetic anionic polymeric        polycarboxylate, e.g., wherein the anionic polymer is selected        from 1:4 to 4:1 copolymers of maleic anhydride or acid with        another polymerizable ethylenically unsaturated monomer; e.g.,        wherein the anionic polymer is a methyl vinyl ether/maleic        anhydride (PVM/MA) copolymer having an average molecular weight        (M.W.) of about 30,000 to about 1,000,000, e.g. about 300,000 to        about 800,000, e.g., wherein the anionic polymer is about 1-5%,        e.g., about 2%, of the weight of the composition.    -   1.39. Any of the preceding compositions further comprising a        breath freshener, fragrance or flavoring.    -   1.40. Any of the forgoing compositions for use to reduce and        inhibit acid erosion of the enamel, clean the teeth, reduce        bacterially-generated biofilm and plaque, reduce gingivitis,        inhibit tooth decay and formation of cavities, and reduce        dentinal hypersensitivity.    -   1.41. Any of the foregoing compositions produced by a process        comprising the step of mixing TBZC and trimethylglycine        hydrochloride in aqueous media.    -   1.42. Any of the foregoing compositions wherein upon dilution        with water, e.g., to a level of 1% of less of zinc relative to        water, a zinc precipitate, e.g. a TBZC precipitate, is formed.

The invention further provides methods to reduce and inhibit aciderosion of the enamel, clean the teeth, reduce bacterially-generatedbiofilm and plaque, reduce gingivitis, inhibit tooth decay and formationof cavities, whiten teeth, and reduce dentinal hypersensitivity,comprising applying an effective amount of a composition of theinvention, e.g., any of Composition 1, et seq. to the teeth.

The invention further provides a method of making a compositioncomprising a TBZC and TMG, e.g., any of Composition 1, et seq.comprising the step of combining TBZC and an orally acceptable acidaddition salt of TMG, e.g., TMG-HCl, in an aqueous medium.

For example, in various embodiments, the invention provides methods to(i) reduce hypersensitivity of the teeth, (ii) to reduce plaqueaccumulation, (iii) reduce or inhibit demineralization and promoteremineralization of the teeth, (iv) inhibit microbial biofilm formationin the oral cavity, (v) reduce or inhibit gingivitis, (vi) promotehealing of sores or cuts in the mouth, (vii) reduce levels of acidproducing bacteria, (viii) to increase relative levels of non-cariogenicand/or non-plaque forming bacteria, (ix) reduce or inhibit formation ofdental caries, (x), reduce, repair or inhibit pre-carious lesions of theenamel, e.g., as detected by quantitative light-induced fluorescence(QLF) or electrical caries measurement (ECM), (xi) treat, relieve orreduce dry mouth, (xii) clean the teeth and oral cavity, (xiii) reduceerosion, (xiv) whiten teeth; (xv) reduce tartar build-up, and/or (xvi)promote systemic health, including cardiovascular health, e.g., byreducing potential for systemic infection via the oral tissues,comprising applying any of Compositions 1, et seq. as described above tothe oral cavity of a person in need thereof, e.g., one or more times perday. The invention further provides Compositions 1, et seq. for use inany of these methods.

The invention further provides the use of TBZC and TMG in free or orallyacceptable salt form, e.g., trimethylglycine hydrochloride, to make anoral care composition, e.g. any of Compositions 1, et. seq.

The invention further provides the use of TBZC together with TMG in freeor orally acceptable salt form to reduce and inhibit acid erosion of theenamel, clean the teeth, reduce bacterially-generated biofilm andplaque, reduce gingivitis, inhibit tooth decay and formation ofcavities, and reduce dentinal hypersensitivity; (ii) the use of a zincamino acid halide precursors selected from (a) tetrabasic zinc chlorideand an amino acid halide, and/or (b) tetrabasic zinc chloride, an aminoacid and optionally halogen acid in the manufacture of a composition toreduce and inhibit acid erosion of the enamel, clean the teeth, reducebacterially-generated biofilm and plaque, reduce gingivitis, inhibittooth decay and formation of cavities, and reduce dentinalhypersensitivity.

It is discovered that the interaction of the zinc and the TMG convertsthe insoluble TBZC to a highly soluble complex. Preferably, the TMG isin acid addition salt form, e.g. hydrochloride form. The complex ishighly soluble at concentrations in water, e.g., levels corresponding toabout 1% or more of zinc. But with increasing dilution in water, e.g.,at concentrations of 0.1 to 1%, e.g. about 0.5%, of zinc in water, thecomplex disassociates, and the zinc ion in the complex reverts toinsoluble forms other than zinc oxide (such as TBZC and zinc hydroxide).In experiments wherein complexes are formed using TBZC and an amino acidsuch as lysine or arginine, precipitation upon dilution is alsoobserved, although at higher dilution levels, but the precipitate iszinc oxide, so the formation of a TBZC precipitate is unexpected.

This dynamic—reduced solubility upon increasing dilution—is unusual andunexpected. The dilution upon brushing or rinsing or combination withsaliva facilitates the deposition of the zinc precipitate on the teethwith administration, which acts to occlude the dentinal tubules, therebyreducing hypersensitivity, and also providing zinc to the enamel, whichreduces acid erosion, biofilm and plaque formation.

It will be understood that although the zinc and TMG may be primarily inthe form of precursor materials (e.g. TBZC and TMG-HCl) or in the formof a complex, there may be some degree of equilibrium, so that theproportion of material which is actually in complex compared to theproportion in precursor form may vary depending on the preciseconditions of formulation, concentration of materials, pH, presence orabsence of water, presence or absence of other charged molecules, and soforth.

The actives can be delivered in the form of any oral care formulations,for example a toothpaste, gel, mouthwash, powder, cream, strip, gum, orany other known in the art.

If the actives are delivered in the form of a mouthwash, a persondesiring the benefits rinses with the stock solution and naturaldilution of the stock solution by saliva will initiate the precipitationof the zinc. Alternatively, the person can mix a stock solution withappropriate amount of an aqueous diluent (e.g. to provide aconcentration of zinc relative to water of about 0.1-1%), and rinse withthe mixture.

In another embodiment, the mixture is prepared and immediatelytransferred into a retaining tray, such as those used in holdingwhitening gels, and the person can wear the tray for the effectiveperiod of time. The teeth that are in contact with the mixture will betreated. For use with retaining tray, the mixture can be in the form ofa low-viscosity liquid or a gel.

In another embodiment, the stock solution, or a mixture of stocksolution with water, is applied to the teeth in a gel formulation, e.g.,wherein the gel can stay on the tooth for an extended period of time foreffective treatment.

In another embodiment, the active is provided in a toothpaste. Uponbrushing, the active is diluted by saliva and water, leading toprecipitation and the formation of deposits and occluding particles.

The rate of precipitation from the formulation can be modulated byadjusting concentration of the complex in the stock solution, andchanging the ratio of the stock to water. A more diluted formula leadsto faster precipitation and is thus preferred when a fast treatment isdesired.

The benefits of the oral care compositions of the invention arenumerous. By providing zinc ions and zinc containing compounds that canrelease zinc ions in oral cavities, the oral care compositions of theinvention provide antimicrobial, antiplaque, antigingivitis,anti-malodor, anticaries, and anticalculus benefits. The occludingparticles and the surface deposits are compounds containing zinc saltswhich can release zinc ions into oral cavities and provide the variousbenefits as recognized above. The coating formed on dental surfaces dueto deposition can enhance the whiteness of the dental surface, thusproviding whitening benefits. Additional benefits include but are notlimited to anti-attachment, anti-periodontitis and anti-bone loss, aswell as promotion of wound healing.

A second benefit is the antierosive properties of zinc ions, which formantierosive deposits on tooth surfaces through oxidation and hydrolysis.The surface deposits, as well as the occluding particles, can react withand neutralize acids, thus protecting the dental surface from theerosive effects of the acids. It is also noted that when the surfacedeposits and occluding particles neutralize acids, beneficial zinc ionscan be released, providing oral care benefits other than anti-erosion.

A third benefit is anti-sensitivity benefit as a result of theocclusion. Occlusion of dentin tubules leads to sensitivity relief.

A fourth benefit is the benefit associated with the TMG. The TMG, due toits zwitterionic character, provides a buffering effect, counteractingthe acid which can damage the teeth and so can provide anticariesbenefits. In addition, TMG has been recognized to provide relief fromdry-mouth.

In a particular embodiment, the invention provides an ionic complexcomprising TBZC, TMG and an anionic species, e.g. a halide, for examplechloride. In a particular embodiment, the invention provides a complexformed by combining TBZC and TMG HCl in an aqueous media to form acomplex conveniently referred to as a TBZC-TMG HCl complex.

In another embodiment, the invention provides oral care formulationscomprising a TBZC-TMG HCl complex, e.g., compositions according toComposition 1, et seq., comprising a TBZC-TMG HCl complex e.g. in theform of a mouthrinse, a gel, a toothpaste, a cream, a powder, a strip,or a gum.

In one embodiment, if the desired formulation is in the form of amouthrinse, a two-component delivery system is contemplated. The firstcomponent is a concentrated solution of the TBZC-TMG HCl complex, andthe second component is substantially water. The two components aremixed by the administrator/user immediately before treatment.Alternatively, a single-component delivery system in the form of amouthrinse is contemplated, where the system comprises a concentratedsolution of the TBZC-TMG HCl complex and the diluent is supplied by theadministrator/user either in the form of water naturally involved in atypical oral care treatment and/or saliva generated by the user.

The invention is also directed, in further embodiments, to a controlledrelease system and a method for delivering zinc ions and TMG over anextended period of time within oral cavities, comprising administering acomposition according to Composition 1, et seq.

In particular embodiments, Compositions 1, et seq. provide complexesfrom TBZC and TMG, for example zinc-TMG-chloride complexes, and/or theTBZC and TMG in free or acid addition salt form, e.g., TMG-HCl, ascomplex precursors, which can react in situ with water to form thecomplexes. The in situ formation provides ease of formulation. Inanother embodiment, the water permitting formation of the complex fromthe precursor comes from saliva and/or rinsing water that comes intocontact with the composition after application.

In a particular embodiment, the TMG is provided in the form of an acidaddition salt, for example a hydrohalide, e.g. trimethylglycinehydrochloride, which forms a complex of complexes in aqueous media withTBZC.

Because the number of moles or weight percent of various zinc salts andcomplexes herein will vary based on the particular salt or complex form,we frequently refer herein to the amount of total zinc in theformulation by weight or by molar amount, irrespective of its salt orcomplex form. In some embodiments, the total amount of zinc in thecomposition is 0.05 to 8% by weight of the composition. In otherembodiments, the total amount of zinc is at least 0.1, at least 0.2, atleast 0.3, at least 0.4, at least 0.5, or at least 1 up to 8% by weightof the composition. In other embodiments, the total amount of zinc inthe composition is less than 5, less than 4, less than 3, less than 2,or less than 1 to 0.05% by weight of the composition. For example, insome embodiments, the total amount of zinc in the composition may beabout 1%.

Active Agents:

The compositions of the invention may comprise various agents which areactive to protect and enhance the strength and integrity of the enameland tooth structure and/or to reduce bacteria and associated tooth decayand/or gum disease, including or in addition to the zinc—aminoacid—halide complexes. Effective concentration of the active ingredientsused herein will depend on the particular agent and the delivery systemused. It is understood that a toothpaste for example will typically bediluted with water upon use, while a mouth rinse typically will not be.Thus, an effective concentration of active in a toothpaste willordinarily be 5-15× higher than required for a mouth rinse. Theconcentration will also depend on the exact salt or polymer selected.For example, where the active agent is provided in salt form, thecounterion will affect the weight of the salt, so that if the counterionis heavier, more salt by weight will be required to provide the sameconcentration of active ion in the final product. Arginine, wherepresent, may be present at levels from, e.g., about 0.1 to about 20 wt %(expressed as weight of free base), e.g., about 1 to about 10 wt % for aconsumer toothpaste or about 7 to about 20 wt % for a professional orprescription treatment product. Fluoride where present may be present atlevels of, e.g., about 25 to about 25,000 ppm, for example about 750 toabout 2,000 ppm for a consumer toothpaste, or about 2,000 to about25,000 ppm for a professional or prescription treatment product. Levelsof antibacterial agents will vary similarly, with levels used intoothpaste being e.g., about 5 to about 15 times greater than used inmouthrinse. For example, a triclosan toothpaste may contain about 0.3 wt% triclosan.

Fluoride Ion Source:

The oral care compositions may further include one or more fluoride ionsources, e.g., soluble fluoride salts. A wide variety of fluorideion-yielding materials can be employed as sources of soluble fluoride inthe present compositions. Examples of suitable fluoride ion-yieldingmaterials are found in U.S. Pat. No. 3,535,421, to Briner et al.; U.S.Pat. No. 4,885,155, to Parran, Jr. et al. and U.S. Pat. No. 3,678,154,to Widder et al. Representative fluoride ion sources include, but arenot limited to, stannous fluoride, sodium fluoride, potassium fluoride,sodium monofluorophosphate, sodium fluorosilicate, ammoniumfluorosilicate, amine fluoride, ammonium fluoride, and combinationsthereof. In certain embodiments the fluoride ion source includesstannous fluoride, sodium fluoride, sodium monofluorophosphate as wellas mixtures thereof. In certain embodiments, the oral care compositionof the invention may also contain a source of fluoride ions orfluorine-providing ingredient in amounts sufficient to supply about 25ppm to about 25,000 ppm of fluoride ions, generally at least about 500ppm, e.g., about 500 to about 2000 ppm, e.g., about 1000 to about 1600ppm, e.g., about 1450 ppm. The appropriate level of fluoride will dependon the particular application. A toothpaste for general consumer usewould typically have about 1000 to about 1500 ppm, with pediatrictoothpaste having somewhat less. A dentifrice or coating forprofessional application could have as much as about 5,000 or even about25,000 ppm fluoride. Fluoride ion sources may be added to thecompositions of the invention at a level of about 0.01 wt. % to about 10wt. % in one embodiment or about 0.03 wt. % to about 5 wt. %, and inanother embodiment about 0.1 wt. % to about 1 wt. % by weight of thecomposition in another embodiment. Weights of fluoride salts to providethe appropriate level of fluoride ion will obviously vary based on theweight of the counterion in the salt.

In various embodiments, the amino acid is present in an amount of about0.5 wt. % to about 20 wt. % of the total composition weight, about 0.5wt. % to about 10 wt. % of the total composition weight, for exampleabout 1.5 wt. %, about 3.75 wt. %, about 5 wt. %, or about 7.5 wt. % ofthe total composition weight in the case of a dentifrice, or for exampleabout 0.5-2 wt. %, e.g., about 1% in the case of a mouthwash.

Abrasives:

The compositions of the invention, e.g. Composition 1 et seq. includesilica abrasives, and may comprise additional abrasives, e.g., a calciumphosphate abrasive, e.g., tricalcium phosphate (Ca₃(PO₄)₂),hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂), or dicalcium phosphate dihydrate(CaHPO₄.2H₂O, also sometimes referred to herein as DiCal) or calciumpyrophosphate; calcium carbonate abrasive; or abrasives such as sodiummetaphosphate, potassium metaphosphate, aluminum silicate, calcinedalumina, bentonite or other siliceous materials, or combinationsthereof.

Other silica abrasive polishing materials useful herein, as well as theother abrasives, generally have an average particle size ranging betweenabout 0.1 and about 30 microns, about between 5 and about 15 microns.The silica abrasives can be from precipitated silica or silica gels,such as the silica xerogels described in U.S. Pat. No. 3,538,230, toPader et al. and U.S. Pat. No. 3,862,307, to Digiulio. Particular silicaxerogels are marketed under the trade name Syloid® by the W.R. Grace &Co., Davison Chemical Division. The precipitated silica materialsinclude those marketed by the J.M. Huber Corp. under the trade nameZeodent®, including the silica carrying the designation Zeodent 115 and119. These silica abrasives are described in U.S. Pat. No. 4,340,583, toWason. In certain embodiments, abrasive materials useful in the practiceof the oral care compositions in accordance with the invention includesilica gels and precipitated amorphous silica having an oil absorptionvalue of less than about 100 cc/100 g silica and in the range of about45 cc/100 g to about 70 cc/100 g silica. Oil absorption values aremeasured using the ASTA Rub-Out Method D281. In certain embodiments, thesilicas are colloidal particles having an average particle size of about3 microns to about 12 microns, and about 5 to about 10 microns. Low oilabsorption silica abrasives particularly useful in the practice of theinvention are marketed under the trade designation Sylodent XWA® byDavison Chemical Division of W.R. Grace & Co., Baltimore, Md. 21203.Sylodent 650 XWA®, a silica hydrogel composed of particles of colloidalsilica having a water content of 29% by weight averaging about 7 toabout 10 microns in diameter, and an oil absorption of less than about70 cc/100 g of silica is an example of a low oil absorption silicaabrasive useful in the practice of the present invention.

Foaming Agents:

The oral care compositions of the invention also may include an agent toincrease the amount of foam that is produced when the oral cavity isbrushed. Illustrative examples of agents that increase the amount offoam include, but are not limited to polyoxyethylene and certainpolymers including, but not limited to, alginate polymers. Thepolyoxyethylene may increase the amount of foam and the thickness of thefoam generated by the oral care carrier component of the presentinvention. Polyoxyethylene is also commonly known as polyethylene glycol(“PEG”) or polyethylene oxide. The polyoxyethylenes suitable for thisinvention will have a molecular weight of about 200,000 to about7,000,000. In one embodiment the molecular weight will be about 600,000to about 2,000,000 and in another embodiment about 800,000 to about1,000,000. Polyox® is the trade name for the high molecular weightpolyoxyethylene produced by Union Carbide. The polyoxyethylene may bepresent in an amount of about 1% to about 90%, in one embodiment about5% to about 50% and in another embodiment about 10% to about 20% byweight of the oral care carrier component of the oral care compositionsof the present invention. Where present, the amount of foaming agent inthe oral care composition (i.e., a single dose) is about 0.01 to about0.9% by weight, about 0.05 to about 0.5% by weight, and in anotherembodiment about 0.1 to about 0.2% by weight.

Surfactants:

The compositions useful in the invention may contain anionicsurfactants, for example:

-   -   i. water-soluble salts of higher fatty acid monoglyceride        monosulfates, such as the sodium salt of the monosulfated        monoglyceride of hydrogenated coconut oil fatty acids such as        sodium N-methyl N-cocoyl taurate, sodium cocomonoglyceride        sulfate,    -   ii. higher alkyl sulfates, such as sodium lauryl sulfate,    -   iii. higher alkyl-ether sulfates, e.g., of formula        CH₃(CH₂)_(m)CH₂(OCH₂CH₂)_(n)OSO₃X, wherein m is 6-16, e.g., 10,        n is 1-6, e.g., 2, 3 or 4, and X is Na or K, for example sodium        laureth-2 sulfate (CH₃(CH₂)₁₀CH₂(OCH₂CH₂)₂OSO₃Na).    -   iv. higher alkyl aryl sulfonates such as sodium dodecyl benzene        sulfonate (sodium lauryl benzene sulfonate)    -   v. higher alkyl sulfoacetates, such as sodium lauryl        sulfoacetate (dodecyl sodium sulfoacetate), higher fatty acid        esters of 1,2 dihydroxy propane sulfonate, sulfocolaurate        (N-2-ethyl laurate potassium sulfoacetamide) and sodium lauryl        sarcosinate.

By “higher alkyl” is meant, e.g., C₆₋₃₀ alkyl. In particularembodiments, the anionic surfactant is selected from sodium laurylsulfate and sodium ether lauryl sulfate. The anionic surfactant may bepresent in an amount which is effective, e.g., >0.01% by weight of theformulation, but not at a concentration which would be irritating to theoral tissue, e.g., <10%, and optimal concentrations depend on theparticular formulation and the particular surfactant. For example,concentrations used or a mouthwash are typically on the order of onetenth that used for a toothpaste. In one embodiment, the anionicsurfactant is present in a toothpaste at from about 0.3% to about 4.5%by weight, e.g., about 1.5%. The compositions of the invention mayoptionally contain mixtures of surfactants, e.g., comprising anionicsurfactants and other surfactants that may be anionic, cationic,zwitterionic or nonionic. Generally, surfactants are those which arereasonably stable throughout a wide pH range. Surfactants are describedmore fully, for example, in U.S. Pat. No. 3,959,458, to Agricola et al.;U.S. Pat. No. 3,937,807, to Haefele; and U.S. Pat. No. 4,051,234, toGieske et al. In certain embodiments, the anionic surfactants usefulherein include the water-soluble salts of alkyl sulfates having about 10to about 18 carbon atoms in the alkyl radical and the water-solublesalts of sulfonated monoglycerides of fatty acids having about 10 toabout 18 carbon atoms. Sodium lauryl sulfate, sodium lauroyl sarcosinateand sodium coconut monoglyceride sulfonates are examples of anionicsurfactants of this type. In a particular embodiment, the composition ofthe invention, e.g., Composition 1, et seq., comprises sodium laurylsulfate.

The surfactant or mixtures of compatible surfactants can be present inthe compositions of the present invention in about 0.1% to about 5.0%,in another embodiment about 0.3% to about 3.0% and in another embodimentabout 0.5% to about 2.0% by weight of the total composition.

Tartar Control Agents:

In various embodiments of the present invention, the compositionscomprise an anticalculus (tartar control) agent. Suitable anticalculusagents include without limitation phosphates and polyphosphates (forexample pyrophosphates), polyaminopropanesulfonic acid (AMPS),hexametaphosphate salts, zinc citrate trihydrate, polypeptides,polyolefin sulfonates, polyolefin phosphates, diphosphonates. Theinvention thus may comprise phosphate salts. In particular embodiments,these salts are alkali phosphate salts, i.e., salts of alkali metalhydroxides or alkaline earth hydroxides, for example, sodium, potassiumor calcium salts. “Phosphate” as used herein encompasses orallyacceptable mono- and polyphosphates, for example, P₁₋₆ phosphates, forexample monomeric phosphates such as monobasic, dibasic or tribasicphosphate; dimeric phosphates such as pyrophosphates; and multimericphosphates, e.g., sodium hexametaphosphate. In particular examples, theselected phosphate is selected from alkali dibasic phosphate and alkalipyrophosphate salts, e.g., selected from sodium phosphate dibasic,potassium phosphate dibasic, dicalcium phosphate dihydrate, calciumpyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate,sodium tripolyphosphate, and mixtures of any of two or more of these. Ina particular embodiment, for example the compositions comprise a mixtureof tetrasodium pyrophosphate (Na₄P₂O₇), calcium pyrophosphate (Ca₂P₂O₇),and sodium phosphate dibasic (Na₂HPO₄), e.g., in amounts of ca. 3-4% ofthe sodium phosphate dibasic and ca. 0.2-1% of each of thepyrophosphates. In another embodiment, the compositions comprise amixture of tetrasodium pyrophosphate (TSPP) and sodium tripolyphosphate(STPP)(Na₅P₃O₁₀), e.g., in proportions of TSPP at about 1-2% and STPP atabout 7% to about 10%. Such phosphates are provided in an amounteffective to reduce erosion of the enamel, to aid in cleaning the teeth,and/or to reduce tartar buildup on the teeth, for example in an amountof 2-20%, e.g., ca. 5-15%, by weight of the composition.

Flavoring Agents:

The oral care compositions of the invention may also include a flavoringagent. Flavoring agents which are used in the practice of the presentinvention include, but are not limited to, essential oils as well asvarious flavoring aldehydes, esters, alcohols, and similar materials.Examples of the essential oils include oils of spearmint, peppermint,wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon,lemon, lime, grapefruit, and orange. Also useful are such chemicals asmenthol, carvone, and anethole. Certain embodiments employ the oils ofpeppermint and spearmint. The flavoring agent may be incorporated in theoral composition at a concentration of about 0.1 to about 5% by weighte.g. about 0.5 to about 1.5% by weight.

Polymers:

The oral care compositions of the invention may also include additionalpolymers to adjust the viscosity of the formulation or enhance thesolubility of other ingredients. Such additional polymers includepolyethylene glycols, polysaccharides (e.g., cellulose derivatives, forexample carboxymethyl cellulose, or polysaccharide gums, for examplexanthan gum or carrageenan gum). Acidic polymers, for examplepolyacrylate gels, may be provided in the form of their free acids orpartially or fully neutralized water soluble alkali metal (e.g.,potassium and sodium) or ammonium salts.

Silica thickeners, which form polymeric structures or gels in aqueousmedia, may be present. Note that these silica thickeners are physicallyand functionally distinct from the particulate silica abrasives alsopresent in the compositions, as the silica thickeners are very finelydivided and provide little or no abrasive action. Other thickeningagents are carboxyvinyl polymers, carrageenan, hydroxyethyl celluloseand water soluble salts of cellulose ethers such as sodium carboxymethylcellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gumssuch as karaya, gum arabic, and gum tragacanth can also be incorporated.Colloidal magnesium aluminum silicate can also be used as component ofthe thickening composition to further improve the composition's texture.In certain embodiments, thickening agents in an amount of about 0.5% toabout 5.0% by weight of the total composition are used.

The compositions of the invention may include an anionic polymer, forexample in an amount of from about 0.05 to about 5%. Such agents areknown generally for use in dentifrice, although not for this particularapplication, useful in the present invention are disclosed in U.S. Pat.Nos. 5,188,821 and 5,192,531; and include synthetic anionic polymericpolycarboxylates, such as 1:4 to 4:1 copolymers of maleic anhydride oracid with another polymerizable ethylenically unsaturated monomer,preferably methyl vinyl ether/maleic anhydride having a molecular weight(M.W.) of about 30,000 to about 1,000,000, most preferably about 300,000to about 800,000. These copolymers are available for example as Gantrez.e.g., AN 139 (M.W. 500,000), AN 119 (M.W. 250,000) and preferably S-97Pharmaceutical Grade (M.W. 700,000) available from ISP Technologies,Inc., Bound Brook, N.J. 08805. The enhancing agents when present arepresent in amounts ranging from about 0.05 to about 3% by weight. Otheroperative polymers include those such as the 1:1 copolymers of maleicanhydride with ethyl acrylate, hydroxyethyl methacrylate,N-vinyl-2-pyrollidone, or ethylene, the latter being available forexample as Monsanto EMA No. 1103, M.W. 10,000 and EMA Grade 61, and 1:1copolymers of acrylic acid with methyl or hydroxyethyl methacrylate,methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.Suitable generally, are polymerized olefinically or ethylenicallyunsaturated carboxylic acids containing an activated carbon-to-carbonolefinic double bond and at least one carboxyl group, that is, an acidcontaining an olefinic double bond which readily functions inpolymerization because of its presence in the monomer molecule either inthe alpha-beta position with respect to a carboxyl group or as part of aterminal methylene grouping. Illustrative of such acids are acrylic,methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxypropionic, sorbic, alpha-chlorsorbic, cinnamic, beta-styrylacrylic,muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic,alpha-phenylacrylic, 2-benzyl acrylic, 2-cyclohexylacrylic, angelic,umbellic, fumaric, maleic acids and anhydrides. Other different olefinicmonomers copolymerizable with such carboxylic monomers includevinylacetate, vinyl chloride, dimethyl maleate and the like. Copolymerscontain sufficient carboxylic salt groups for water-solubility. Afurther class of polymeric agents includes a composition containinghomopolymers of substituted acrylamides and/or homopolymers ofunsaturated sulfonic acids and salts thereof, in particular wherepolymers are based on unsaturated sulfonic acids selected fromacrylamidoalykane sulfonic acids such as 2-acrylamide 2 methylpropanesulfonic acid having a molecular weight of about 1,000 to about2,000,000, described in U.S. Pat. No. 4,842,847, Jun. 27, 1989 to Zahid.Another useful class of polymeric agents includes polyamino acidscontaining proportions of anionic surface-active amino acids such asaspartic acid, glutamic acid and phosphoserine, e.g. as disclosed inU.S. Pat. No. 4,866,161 Sikes et al.

Water:

The oral compositions may comprise significant levels of water. Wateremployed in the preparation of commercial oral compositions should bedeionized and free of organic impurities. The amount of water in thecompositions includes the free water which is added plus that amountwhich is introduced with other materials.

Humectants:

Within certain embodiments of the oral compositions, it is alsodesirable to incorporate a humectant to prevent the composition fromhardening upon exposure to air. Certain humectants can also impartdesirable sweetness or flavor to dentifrice compositions. Suitablehumectants include edible polyhydric alcohols such as glycerine,sorbitol, xylitol, propylene glycol as well as other polyols andmixtures of these humectants. In one embodiment of the invention, theprincipal humectant is glycerin, which may be present at levels ofgreater than 25%, e.g. 25-35% about 30%, with 5% or less of otherhumectants.

Other Optional Ingredients:

In addition to the above-described components, the embodiments of thisinvention can contain a variety of optional dentifrice ingredients someof which are described below. Optional ingredients include, for example,but are not limited to, adhesives, sudsing agents, flavoring agents,sweetening agents, additional antiplaque agents, abrasives, and coloringagents. These and other optional components are further described inU.S. Pat. No. 5,004,597, to Majeti; U.S. Pat. No. 3,959,458 to Agricolaet al. and U.S. Pat. No. 3,937,807, to Haefele, all being incorporatedherein by reference.

Unless stated otherwise, all percentages of composition components givenin this specification are by weight based on a total composition orformulation weight of 100%.

Unless otherwise specifically identified, the ingredients for use in thecompositions and formulations of the present invention are preferablycosmetically acceptable ingredients. By “cosmetically acceptable” ismeant suitable for use in a formulation for topical application to humanskin. A cosmetically acceptable excipient, for example, is an excipientwhich is suitable for external application in the amounts andconcentrations contemplated in the formulations of this invention, andincludes for example excipients which are “Generally Recognized as Safe”(GRAS) by the United States Food and Drug Administration.

The compositions and formulations as provided herein are described andclaimed with reference to their ingredients, as is usual in the art. Aswould be evident to one skilled in the art, the ingredients may in someinstances react with one another, so that the true composition of thefinal formulation may not correspond exactly to the ingredients listed.Thus, it should be understood that the invention extends to the productof the combination of the listed ingredients.

As used throughout, ranges are used as shorthand for describing each andevery value that is within the range. Any value within the range can beselected as the terminus of the range. In addition, all references citedherein are hereby incorporated by referenced in their entireties. In theevent of a conflict in a definition in the present disclosure and thatof a cited reference, the present disclosure controls.

Unless otherwise specified, all percentages and amounts expressed hereinand elsewhere in the specification should be understood to refer topercentages by weight. The amounts given are based on the active weightof the material.

EXAMPLES Example 1

It is shown that TBZC can react with TMG HCl and produce soluble formsof zinc species, conveniently named TBZC-TMG HCl. Surprisingly, TBZC-TMGHCl is found to produce solid material upon dilution with appropriateamount of water. The solid material is present in the form of aprecipitate or flocculation, and attaches to a dental surface if thedental surface is exposed to the reaction mixture. The solid material isalso expected to be attachable to the soft tissues within an oral carecavity. The ability of TBZC-TMG HCl in formingflocculation/precipitation is unique and unexpected.

TBZC-TMG, without the acidification, solubilizes but fails to generateprecipitation/flocculation upon dilution. Therefore, where precipitationupon dilution is desired, it is preferred that acid be present, eitherby addition or by providing the TMG in the form of an acid additionsalt. Other complexes with related structures are tested and fail togenerate precipitation/flocculation with or without acidification. Amongthese are TBZC-cetyl pyridinium chloride (CPC), TBZC-CPC HCl (withpartial HCl, meaning the molar ratios of HCl vs. CPC is less than 1),TBZC-Creatine, TBZC-Creatine HCl (both with partial HCl and equal molesof HCl).

Stable solutions of complexes are prepared and characterized. Thesecomplexes include TBZC-TMG, TBZC-TMG HCl, TBZC-CPC, TBZC-CPC HCl(partial HCl), TBZC-Creatine, and TBZC-Creatine HCl (2 types):

Sample 1, TBZC-TMG, is prepared as follows. At room temperature, 5.5178g (0.01 mol) of TBZC powder is slowly added into 50 mL of TMG solution(5.8577 g, 0.05 mol of TMG in 50 ml DI water). The mixture is stirredovernight for about 20 hours. Unreacted TBZC is removed by centrifugingfollowed by filtering through a 0.45 micron membrane. The final productis a transparent solution. Zinc concentration is determined by atomicabsorption spectroscopy after acid digestion.

TABLE 1 SAMPLE 1 TBZC TMG Amount added 5.5178 g, 0.01 mol 5.8577 g, 0.05mol pH of final solution 6.84 Zn content in solution 0.13 wt % (w/w %)

Sample 2, TBZC-TMG, is prepared as follows. At room temperature, 5.5193g (0.01 mol) of TBZC powder is slowly added into 50 mL of TMG solution(5.8573 g, 0.05 mol of TMG in 50 ml DI water). The mixture is stirredovernight for about 20 hours. Unreacted TBZC is removed by centrifugingfollowed by filtering through a 0.45 micron membrane. The final productis a transparent solution. Zinc concentration is determined by atomicabsorption spectroscopy after acid digestion.

TABLE 2 SAMPLE 2 TBZC TMG Amount added 5.5193 g, 0.01 mol 5.8573 g, 0.05mol pH of final solution 6.83 Zn content in solution 0.13 wt % (w/w %)

Sample 3, TBZC-TMG HCl, is prepared as follows. At room temperature,5.5188 g (0.01 mol) of TBZC powder is slowly added into 50 mL of TMGsolution (7.68 g, 0.05 mol of TMG HCl in 50 ml DI water). The mixture isstirred overnight for about 20 hours. Unreacted TBZC is removed bycentrifuging followed by filtering through a 0.45 micron membrane. Thefinal product is a transparent solution. Zinc concentration isdetermined by atomic absorption spectroscopy after acid digestion.

TABLE 3 SAMPLE 3 TBZC TMG HCl Amount added 5.5188 g, 0.01 mol 7.68 g,0.05 mol pH of final solution 5.43 Zn content in solution 3.42 wt %

Sample 4, TBZC-TMG HCl, is prepared as follows. At room temperature,5.5207 g (0.01 mol) of TBZC powder is slowly added into 50 mL of TMGsolution (7.6804 g, 0.05 mol of TMG HCl in 50 ml DI water). The mixtureis stirred overnight for about 20 hours. Unreacted TBZC is removed bycentrifuging followed by filtering through a 0.45 micron membrane. Thefinal product is a transparent solution. Zinc concentration isdetermined by atomic absorption spectroscopy after acid digestion.

TABLE 4 SAMPLE 4 TBZC TMG HCl Amount added 5.5207 g, 0.01 mol 7.6804 g,0.05 mol pH of final solution 5.79 Zn content in solution 3.77 wt %

Sample 5, TBZC-Creatine, is prepared as follows. At room temperature,5.5183 g (0.01 mol) of TBZC powder is slowly added into 50 mL ofcreatine monohydrate solution (7.4595 g, 0.05 mol of creatinemonohydrate in 50 ml DI water). Sonication is employed to facilitate thedissolution. The mixture is stirred overnight for about 20 hours.Unreacted TBZC is removed by centrifuging followed by filtering througha 0.45 micron membrane. The final product is a transparent solution.Zinc concentration is determined by atomic absorption spectroscopy afteracid digestion.

TABLE 5 SAMPLE 5 TBZC Creatine Monohydrate Amount added 5.5183 g, 0.01mol 7.4595 g, 0.05 mol pH of final solution 6.89 Zn content in solution0.04 wt %

Sample 6, TBZC-Creatine 1/3 HCl, is prepared as follows. CreatineMonohydrate is added into HCl aqueous solution with stirring at roomtemperature. TBZC is then added after about 15 minutes. The suspensionis centrifuged at 7200 rpm for 30 mins followed by filtering through0.45 micron membrane. Transparent solution is collected, and unreactedwhite solid is discarded. Zinc concentration is determined by atomicabsorption spectroscopy after acid digestion.

TABLE 6 SAMPLE 6 Creatine HCl (33 wt % TBZC Monohydrate solution) Amountadded 5.5201 g, 7.4648 g, 1.839 g, 0.01 mol 0.05 mol 0.0166 mmol pH offinal solution 5.91 Zn content in solution 1.26 wt %

Sample 7, TBZC-CPC, is prepared as follows. At room temperature, 5.5183g (0.01 mol) of TBZC powder is slowly added into 50 mL of cetylpyridinium chloride solution (17.8998 g, 0.05 mol of cetyl pyridiniumchloride in 50 ml DI water). Sonication is employed to facilitate thedissolution. The mixture is stirred overnight for about 20 hours.Unreacted TBZC is removed by centrifuging followed by filtering througha 0.45 micron membrane. The final product is a transparent solution.Zinc concentration is determined by atomic absorption spectroscopy afteracid digestion.

TABLE 7 SAMPLE 7 TBZC cetyl pyridinium chloride Amount added 5.5183 g,0.01 mol 17.8998 g, 0.05 mol pH of final solution 7.48 Zn content insolution 0.03 wt %

Sample 8, TBZC-CPC 1/3 HCl, is prepared as follows. Cetyl pyridiniumchloride is added into HCl aqueous solution with stirring at roomtemperature. TBZC is then added after about 15 minutes. The suspensionis centrifuged at 7200 rpm for 30 mins followed by filtering through0.45 micron membrane. Transparent solution is collected, and unreactedwhite solid is discarded. Zinc concentration is determined by atomicabsorption spectroscopy after acid digestion.

TABLE 8 SAMPLE 8 cetyl pyridinium HCl (33 wt % TBZC chloride solution)Amount added 5.5199 g, 17.913 g, 1.820 g, 0.01 mol 0.05 mol 0.0164 mmolpH of final solution 6.91 Zn content in solution 0.04 wt %

Sample 9, TBZC-Creatine HCl, with equal moles of HCl as Creatine, isprepared as follows. Creatine Monohydrate is added into HCl aqueoussolution with stirring at room temperature. After complete dissolutionis achieved, TBZC is added, and a suspension resulted. The suspension iscentrifuged at 7200 rpm for 30 mins followed by filtering through 0.45micron membrane. Transparent solution is collected, and unreacted whitesolid is discarded. Zinc concentration is to be determined by atomicabsorption spectroscopy after acid digestion.

TABLE 9 SAMPLE 9 Creatine HCl (33 wt % TBZC Monohydrate solution) Amountadded 5.5201 g, 7.4587 g, 5.57 g, 0.01 mol 0.05 mol 0.0504 mmol pH offinal solution 5.55 Zn content in solution TBD

Attempts are made to prepare TBZC-CPC HCl, with equal moles of HCl asCPC. Cetyl Pyrindium is added into HCl aqueous solution under stirringat temperature, and white suspension is formed (it does not totallydissolve after being stirred for 15 mins). Then TBZC is added. Afterbeing stirring for a while, the mixture became “soft solid” which is notable to be stirred anymore. The experiment is then abandoned.

TABLE 10 SAMPLE 10 cetyl pyridinium HCl (33 wt % TBZC chloride solution)Amount added 5.5174 g, 17.913 g, 5.66 g, 0.01 mol 0.05 mol 0.0511 mmolpH of final solution Not applicable. Zn content Not applicable.

For the preparation involving CPC HCl (TBZC-CPC 1/3 HCl, Sample 8), HClis added in 1:3 molar ratios (HCl:CPC). When HCl is added in equalnumber of moles as CPC, the reaction mixture is a thick slurry and noliquid can be extracted.

For the preparations involving Creatine HCl, two types are made. A firsttype involved use of HCl in 1:3 molar ratios to creatine and the sampleis coded TBZC-Creatine 1/3 HCl, i.e., Sample 6. A second type involveduse of HCl in 1:1 molar ratio to creatine and the sample is codedTBZC-Creatine HCl, i.e, Sample 9.

Each complex is evaluated for its ability and rate to form precipitationor flocculation upon dilution. For this analysis, samples with variousdilution ratios (for example, 2× through 32×) are prepared and kept at37° C. The samples are monitored periodically and their efficiency ofgenerating precipitation/flocculation are recorded.

Dilutions experiments indicate that TBZC-TMG HCl is the only one capableof generating precipitation/flocculation, and thus is preferred fordepositing solid particles on dentine surface. Rate offlocculation/precipitation depends on the dilution ratio, which isrelated to the initial zinc concentration at the time water is mixedwith the stock solutions in desired proportions.

A first dilution experiment is carried out using the batch of sampleTBZC-TMG HCl with a zinc concentration of 3.77 wt %. Dilutions areprepared with initial zinc concentrations (prior to precipitation) at0.118 wt %, 0.236 wt %, 0.471 wt %, 0.628 wt %, 0.942 wt % and 1.88 wt%. The diluted samples are kept at 37° C., and the rates at whichflocculation/precipitation occurred are monitored. Dilutions withinitial zinc concentrations at 0.471 wt %, 0.628 wt % and 0.942 wt % areable to generate some visible flocculation within a couple of minutesfrom the time point when the stock solution is mixed with water. Onehour from mixing, visible flocculation are observed in dilutions withinitial zinc concentrations of 0.236 wt %, 0.471 wt %, 0.628 wt %, and0.942 wt %. After 20 hours, flocculation and precipitation could beobserved in all samples.

A second dilution experiment is carried out using the batch of sampleTBZC-TMG HCl with a zinc concentration of 3.42 wt %. Dilutions areprepared with initial zinc concentrations at 0.107 wt %, 0.214 wt %,0.428 wt %, 0.855 wt %, and 1.71 wt %. The diluted samples are kept at37° C. for about 24 hours and subsequently inspected. Samples withinitial zinc concentrations of 0.428 wt %, 0.855 wt % and 1.71 wt % areable to generate flocculation/precipitation. Samples with initial zincconcentrations of 0.107 wt % and 0.214 wt % fail to generate any visibleamounts of flocculation/precipitation, even after 24 hours ofincubation.

Preparations that generate flocculation/precipitation can be utilized todeposit active agents onto oral surfaces, including dental and mucosalsurfaces. In this regard, dilutions with initial zinc concentrationsbetween about 0.118 wt % through about 1.88 wt % relative to water canbe utilized. In an actual formulation, of course, the concentration ofzinc in the formulation would be lower than the dilution concentrationrelative to water, because the total formulation would comprisecomponents in addition to water. Preparations at the low and high endsof the concentration spectrum tend to require longer hours of treatmentand are not among the most reliable in producingprecipitation/flocculation. Dilutions with initial zinc concentrationsbetween about 0.236 wt % and about 0.942 wt % relative to water arepreferred due to their ability to generate precipitation/flocculationwithin one hour. Dilutions with initial zinc concentration between about0.471 wt % and about 0.942 wt % relative to water are more preferred dueto their ability to generate flocculation within a couple of minutesfrom the onset of dilution.

Preparations that do not generate flocculation/precipitation discernibleto the naked eyes may also be used for depositing active agents ontooral surfaces. The failure to generate noticeableflocculation/precipitation may be due to unfavorable dilution ratio orinadequate treatment duration. However, the preparations may still beable to generate particles, such as colloidal particles. While theseparticles do not form precipitates within the treatment duration, theymay form surface deposits onto oral surfaces. In this regard, theoperable ranges of dilution ratios and/or treatment durations are widerthan what can be directly inferred from the above-mentioned dilutionexperiments.

TBZC-TMG-HCl provides relatively high levels of solubilized zinc, asseen from the data for samples 3 and 4 above, and moreover providesprecipitation/flocculation upon dilution.

The other samples are diluted and fail to generateprecipitation/flocculation with or without acidification. The ability ofTBZC-TMG HCl in generating flocculation/precipitation, unique among theformulations tested, is unexpected. The presence of an anion, e.g., froma TMG acid addition salt form, or provided separately as an acid,enhances performance in this respect. The TBZC-CPC and TBZC-CPC 1/3 HClsamples does not exhibit precipitation upon dilution, suggesting thatthe ability to form flocculation/precipitation is not common to everystructure containing a quaternary amine moiety. The TBZC-Creatine,TBZC-Creatine 1/3 HCl and TBZC-Creatine HCl samples also do not exhibitprecipitation upon dilution, suggesting that the ability to formflocculation/precipitation is not common to all structures with stronglybasic moieties. The failure with TBZC-Creatine 1/3 HCl, which has asubstantial zinc loading and a pH value essentially the same as theTBZC-TMG-HCl, further attests to the uniqueness of TBZC-TMG-HCl. It isalso surprising that TBZC-TMG (without acidification) does not work inproducing precipitates. Without acidification, it can be seen that TMGhas a very limited ability to solubilize TBZC. In addition, TMG isprimarily present in TBZC-TMG as its monomer and oligomers, instead ofbeing in complex with the zinc-containing ions as seen withTBZC-TMG-HCl.

Example 2

TBZC-TMG-HCl complex solutions as described in the preceding example areshown to be effective in occluding dentinal tubules when applied to theteeth and diluted to trigger precipitation. This deposition and tubuleocclusion should reduce sensitivity and furthermore provides a reservoirof zinc to help protect the enamel against erosion and bacterialcolonization.

Thin slices of human dentin sections are prepared following establishedprocedures from whole human teeth. The dentine slices are prepared bycutting human tooth into thin dentine sections of about 800 microns inthickness, designating a test side, sanding said test side using asandpaper of about 600 grit, polishing said test side using a Buehlerpolishing cloth and 5 micron Buehler aluminum oxide, acid-etching saiddentine section in 1% (by weight) citric acid solution for about 20seconds, sonicating said dentine section for 10 minutes, and storingsaid dentine section in phosphate buffered saline (PBS, pH 7.4, GibcoCat. No. 10010).

The thin slices of human dentin sections are first imaged on theconfocal microscope for baseline characterization. Top view images aretaken in XYZ mode, and side view images are taken in XZY mode. Typicalimages are taken with a 50× objective lens, and with ×4 zoom (digitalmagnification). When a more global view is desired at lowermagnification, the images are taken at ×1 or ×1.6 zoom for top viewimages and ×1.6 zoom for side view images.

The thin slices of human dentin sections are then treated using therespective treatment solutions. The stock solutions of TBZC-TMG HCl(with 3.42 wt % of zinc) are first mixed in a vial with the appropriateamount of water in 1:3 ratios by volume, yielding a 0.855 wt % startingzinc concentration. Within seconds, the dentin slice is added to thevial and the vial is capped and stored in an incubator at 37° C. for 1hour for treatment. At the conclusion of the treatment, the vial isremoved from the incubator, and the liquid and precipitate, if any, areremoved using a pipettor. The dentine disc is rinsed for 4 times, eachtime using 1 mL of PBS (pH=7.4) solution. The dentine disc is driedusing a tissue.

The treated thin slices are examined under the confocal microscope forsigns of occlusion and deposition on the surface. Repeat treatments aremade on the treated discs using the same treatment procedure as theprior treatment. Confocal images are taken to monitor the progress ofadditional occlusion and deposition after one or more repeat treatments.

TBZC-TMG HCl, as documented by confocal images, is shown tosubstantially completely occlude the dentin tubules and form asubstantially complete coverage on the surface of the dentin slice,after the 1 hour treatment.

Baseline images indicate open tubules and clean surface between theopenings. Upon a single treatment, significant tubule occlusion can beobserved, as well as substantial deposition between the tubule openings.Two spots are examined under the confocal microscope. At the first spot,both side view and top view images indicated presence of deposition andocclusion, as confirmed on images taken at lower resolution (showinglarger area). At the second spot, almost complete surface deposition andocclusion are observed.

Upon the second treatment, more significant tubule occlusion and surfacedeposition are observed. Side view images indicate complete coverage onthe surface, including tubule openings. Top view images indicatesubstantially complete surface coverage and tubule occlusion, except inisolated patches. A side view image shows a flare of surface depositextending upward from the baseline (either the dentine surface or thetop surface of the deposits in adjacent area) for a height of about 10microns.

After the third treatment, substantial surface deposition and tubuleocclusion are observed. Both the top view and side view images indicatesome patches of open dentine surface and tubules, but the coverage issubstantial nonetheless. It is also worth noting that the tubules thatseemed open are likely still blocked at a depth that eludes the confocalimages.

The significant increase in deposition/occlusion with repeatedtreatments, particularly from the first treatment to the secondtreatment, suggests that the surface of the dentine disc is conditionedby prior treatments and may receive more deposits/occludants duringsubsequent treatments. The result from the third treatment mightindicate a point of saturation. In contrast, repeated treatments usingTBZC-TMG fail to generate surface deposits or tubule occlusion visiblein confocal images.

The treatment duration can be reduced from the one hour period used inthis assay. As noted previously in the dilution experiments, TBZC-TMGHCl preparation with initial zinc concentrations in the range of about0.45 wt % and about 0.95 wt % in water produces visible amounts offlocculation/precipitation within minutes from initial mixing of waterand the stock solution. Also, in the 1-hour treatment study, cloudinessis observed in the solution (with 0.855 wt % initial zinc concentrationin water) within one minute from mixing water and the stock solution.Therefore, these short treatment durations e.g. 1 minute or less can beemployed. These short treatment periods enable many delivery platformsthat are not practical with the 1-hour treatment, such as toothpaste andmouthrinse. Any potential reduction in efficacy in depositing particlesis compensated by more repeated treatments. For example, the treatmentregimen can comprise 3 or more treatments, each lasting about 1 to 2minutes.

Treated dentine discs are also characterized using ESCA (ElectronSpectroscopy for Chemical Analysis) to ascertain the presence and natureof zinc, as well as the presence of TMG. In addition, free-standingprecipitates from TBZC-TMG HCl dilutions are prepared and characterizedusing ESCA.

The compositions of the precipitates were examined both as free-standingentities and as a coating on the dentine surface, using ESCA. The datasuggest that the precipitates comprise a combination of zinc containingcompounds and varying amounts of betaine.

ESCA analysis is conducted on precipitates from TBZC-TMG HCl dilutions,both as prepared and after rinsing with deionized water. Both samplescontain significant amounts of Cl (chlorine). The rinsed sample iscomposed of TBZC, Zn(OH)₂, as well as other zinc species, and no TMG isfound in the rinsed sample. The as-prepared sample contains a mixture ofTBZC and Zn(OH)₂, as well as other zinc species. In addition, theas-prepared sample contained small amounts of TMG. ZnO does not appearas a primary form of zinc in either the rinsed or as-preparedprecipitates, which is in contrast to experiments with TBZC-amino acidcomplexes.

ESCA results also indicate the presence of Zn-containing compounds(phosphate as well as at least one more form of Zn-containing compound)on the dentine disc treated with TBZC-TMG HCl. Zn is detected atsignificant levels (15.07 vs. 0 from baseline). Phosphorus (P) is alsodetected at levels significantly higher than for untreated disks (8.75vs. 1.92 or 2.09 from baseline), suggesting that at least some Zn ispresent as a phosphorus-containing compound on the surface. The Zn peaksare not consistent with Zn in the form of Zn₃(PO₄)₂. Thus the datasuggest that Zn is present as a phosphate, but not orthophosphate. Therelative amounts of Zn and P also suggest that at least one more form ofZn is present on the disk, in addition to phosphate. The data do notsuggest the presence of ZnO.

ESCA analysis does not show the presence of TMG on the dentine disctreated with TBZC-TMG HCl. Nitrogen (N) atom was also detected on thesurface of the disks at levels lower than those for untreated disks(3.55 vs. 13.77 or 14.51 from baseline), reflecting the Zn coating onthe surface. The nitrogen detected is probably from the dentin, since itis present in an uncharged state. TMG nitrogen would be detected as N⁺on the surface, and its presence is not apparent. SIMS analysis fails toindicate any TMG. ESCA detects chemical compositions on the externalsurface of the depositing particles and TMG may be present under theexternal surface, thus eluding detection. Differential in the organiccontents between surface layer and the bulk of the deposit is observedwith TBZC-amino acid preparations and such differential could bereasonably expected in the case of TBZC-TMG. This differential can beattributed to depletion of organic contents from the surface layer uponrinsing. The absence of TMG in the rinsed precipitates and the presenceof TMG in the as-prepared precipitates are supportive of this notion.

TBZC-TMG in the absence of anion does not provide significant depositsto dentin following dilution, in contrast to TBZC-TMG HCl. ESCA analysisshows the presence of only minor amount of zinc-containing compound, andno TMG on the dentine surface treated with TBZC-TMG. The C, O and Nlevels are similar to those for untreated disks indicating littledeposition on the surface. Zn is detected at a low level, indicatingminor uptake from the treatment. P is detected at a slightly elevatedlevel relative to untreated disks, suggesting that Zn may be present onthe surface as a phosphate. The Zn peaks are not consistent with Znbeing present as Zn₃(PO₄)₂, however. The Zn peaks also indicate that Znis not present as ZnO. SIMS analysis fails to discover any TMG. Thuswhere deposition of the zinc upon dilution is desired, anion may beprovided as acid addition salt or as added acid approximately equimolarto TMG.

Example 3

Test dentifrice comprising TBZC-TMG HCl, 1450 ppm fluoride, andphosphates is prepared as follows:

TABLE 11 Ingredient Wt % PEG600 3 CMC-7 0.65 Xanthan 0.2 Sorbitol 27Glycerin 20 Saccharin 0.3 Tetrasodium pyrophosphate 0.5 Calciumpyrophosphate 0.25 Sodium phosphate dibasic 3.5 Sodium fluoride 0.32Titanium dioxide 0.5 Abrasive silica 8 Thickener silica 8 TMG-HCl 5Sodium lauryl sulfate 1.5 Flavoring 1.2 TBZC 2 Water QS

Example 4

A stable mouthwash formulation is provided as follows:

TABLE 12 Ingredient Wt % Sorbitol 7.5 Glycerin 7.5 Propylene glycol 7Sodium saccharin 0.02 Citric acid (anhydrous) 0.05 TBZC 2 TMG HCl 5Flavor/dye 0.12 Potassium sorbate 0.05 Cocamidopropyl betaine 1 Water QS

While the invention has been described with respect to specific examplesincluding presently preferred modes of carrying out the invention, thoseskilled in the art will appreciate that there are numerous variationsand permutations of the above described systems and techniques. It is tobe understood that other embodiments may be utilized and structural andfunctional modifications may be made without departing from the scope ofthe present invention. Thus, the scope of the invention should beconstrued broadly as set forth in the appended claims.

The invention claimed is:
 1. An oral care composition comprising aneffective amount of an ionic complex of a tetrabasic zinc halide andtrimethylglycine (TMG), in free or orally acceptable salt form, whereinthe complex is solubilized in the composition, but provides a zincprecipitate upon dilution in the oral cavity by brushing, rinsing orcombining with saliva.
 2. The composition of claim 1, wherein the halideis selected from chloride, bromide and fluoride.
 3. The composition ofclaim 1, wherein the halide is chloride.
 4. The composition of claim 1wherein the TMG is provided in orally acceptable acid addition saltform.
 5. The composition of claim 1 wherein the TMG is provided in theform of the hydrochloride salt.
 6. The composition of claim 1 whereinthe amount of zinc is 0.05-4% by weight of the composition.
 7. Thecomposition of claim 1 wherein the complex of the tetrabasic zinc halideand TMG is prepared prior to incorporation in the oral care composition.8. The composition of claim 1 in the form of a toothpaste, gel,mouthwash, powder, cream, strip, or gum.
 9. The composition of claim 1further comprising an effective amount of a fluoride ion source.
 10. Thecomposition of claim 1 further comprising an orally acceptable basecomprising ingredients selected from an abrasive, a buffering agent, ahumectant, a surfactant, a thickener, a gum strip or fragment, a breathfreshener, a flavor, a fragrance, a colorant, an antibacterial agent, awhitening agent, an agent that interferes with or prevents bacterialattachment, a calcium source, a phosphate source, an orally acceptablepotassium salt, an anionic polymer, and combination of two or morethereof.
 11. The composition of claim 1 wherein the pH of thecomposition is from pH 5 to pH
 6. 12. A method of manufacturing an oralcare product comprising a composition according to claim 1, comprisingthe step of adding the tetrabasic zinc halide together with TMG, in freeor orally acceptable salt form, to form an ionic complex, duringmanufacture.
 13. A method of treating or reducing dental enamel erosion,cleaning the teeth, reducing bacterially-generated biofilm and plaque,reducing gingivitis, inhibiting tooth decay and formation of cavities,and/or reducing dentinal hypersensitivity comprising applying acomposition according to claim 1 to the teeth.